Luteinizing hormone releasing hormone (LHRH) and agonists thereof have been reported to act as pro-fertility agents in the sense that they induce ovulation in the female. They have been considered also anti-fertility agents because they hyper-stimulate the hypophysial-ovarian steroid axis and prevent implantation of a fertile ovum and maintenance of pregnancy. Corbin et al., End. Res. Comm. 2, 445-458(1975) and 3, 359-376(1976). It is currently believed that these hypothalamic hormones are effective because they trigger the release of luteinizing hormone (LH) from the pituitary, which hormone in turn causes luteolysis, either functional and/or physical, of the corpora lutea (CL) resulting in diminished progesterone release, Hilliard et al., Fert./Steril. 27 421(1976). Depending upon the time of administration, follicle stimulating hormone (FSH) and estradiol-17.beta. (E.sub.2) levels may be elevated and reduced, respectively, Beattie et al. Biol. Reprod. 16 322(1977). This disruption of normal maternal hormone levels creates a state of incompatability between the fertilized ova and the uterus both prior to and after implantation. To reach that state of abnormal maternal hormone level which assures contraception in actual practice, it is necessary to introduce LHRH or an agonist into the maternal circulation via repeated administration over several days.
LHRH and it's agonists have no direct effect on the uterus of the adult female animal, Humphrey et al., Bio. of Reproduction 19 84-91(1978). The contraceptive application of LHRH and agonists in mechanisms directly involving the pituitary-ovarian steroid axis via the maternal blood system. Although there have been reports of effective anti-pregnancy treatments with single systemic treatments in test models, for practical purposes involving the impossibility of determining that critical point in time when a single systemic administration would be effective in actual practice, repeated dosing over a period of several days has been generally required to insure contraception. Continuous systemic administration of LHRH or an agonist by rectal or vaginal absorption to obtain the desired blood levels necessary to induce ovulation is reported in U.S. Pat. No. 3,917,825.
An LHRH agonist is a compound closely resembling LHRH in structure which operates on the same receptor sites to mimic the activity of LHRH. Examples of a few LHRH agonists known to the art are:
[D-Trp.sup.6 ]LHRH PA0 [D-Trp.sup.6 -des-Gly-NH.sub.2.sup.10 ]LHRH ethylamide PA0 [D-Trp.sup.6 -N-Me-Leu.sup.7, des-Gly-NH.sub.2.sup.10 ]LHRH ethylamide PA0 [D-Ala.sup.6 -N-Me-Leu.sup.7, des-Gly-NH.sub.2.sup.10 ]LHRH ethylamide and PA0 [D-Ala.sup.6, des-Gly-NH.sub.2.sup.10 ]LHRH ethylamide.